The purpose of this study was to learn more about the natural history of encephalomyocarditis (EMC) virus and its human disease potential. Results indicate that although many rats (Rattus species) are naturally infected with EMC virus, they do not usually develop an intestinal carrier state and are probably not the virus reservoir, as generally presumed. Serologic studies on selected human populations in various regions of the world show that the prevalence of EMC virus neutralizing antibodies varies widely, from about 1 to 51%. The age-specific antibody rates suggest that infection occurs primarily during childhood. Sera from diabetic, suspected encephalitis and myocarditis patients were examined for EMC antibodies. No association was demonstrated between EMC infection and these 3 diseases. The results suggest that most human cases of EMC infection are probably asymptomatic or unrecognized.